Abstract

Background

Carbon nanotubes (CNT) and carbon nanofibers (CNF) are allotropes of carbon featuring
fibrous morphology. The dimensions and high aspect ratio of CNT and CNF have prompted
the comparison with naturally occurring asbestos fibers which are known to be extremely
pathogenic. While the toxicity and hazardous outcomes elicited by airborne exposure
to single-walled CNT or asbestos have been widely reported, very limited data are
currently available describing adverse effects of respirable CNF.

Results

Here, we assessed pulmonary inflammation, fibrosis, oxidative stress markers and systemic
immune responses to respirable CNF in comparison to single-walled CNT (SWCNT) and
asbestos. Pulmonary inflammatory and fibrogenic responses to CNF, SWCNT and asbestos
varied depending upon the agglomeration state of the particles/fibers. Foci of granulomatous
lesions and collagen deposition were associated with dense particle-like SWCNT agglomerates,
while no granuloma formation was found following exposure to fiber-like CNF or asbestos.
The average thickness of the alveolar connective tissue - a marker of interstitial
fibrosis - was increased 28 days post SWCNT, CNF or asbestos exposure. Exposure to
SWCNT, CNF or asbestos resulted in oxidative stress evidenced by accumulations of
4-HNE and carbonylated proteins in the lung tissues. Additionally, local inflammatory
and fibrogenic responses were accompanied by modified systemic immunity, as documented
by decreased proliferation of splenic T cells ex vivo on day 28 post exposure. The accuracies of assessments of effective surface area for
asbestos, SWCNT and CNF (based on geometrical analysis of their agglomeration) versus
estimates of mass dose and number of particles were compared as predictors of toxicological
outcomes.

Conclusions

We provide evidence that effective surface area along with mass dose rather than specific
surface area or particle number are significantly correlated with toxicological responses
to carbonaceous fibrous nanoparticles. Therefore, they could be useful dose metrics
for risk assessment and management.